Platinated copper(3-clip-phen) complexes as effective DNA-cleaving and cytotoxic agents

The synthesis and biological activity of three heteronuclear platinum-copper complexes based on 3-Clip-Phen are reported. These rigid complexes have been designed to alter the intrinsic mechanism of action of both the platinum moiety and the Cu(3-Clip-Phen) unit. The platinum centers of two of these complexes are coordinated to a 3-Clip-Phen moiety, an ammine ligand and two chlorides, which are either cis or trans to each other. The third complex comprises two 3-Clip-Phen units and two chloride ligands bound in a trans fashion to the platinum ion. DNA-cleavage experiments show that the complexes are highly efficient nuclease agents. In addition, a markedly difference in their aptitude to perform direct double-strand cleavage is observed, which appears to be strongly related to the ability of the platinum unit to coordinate to DNA. Indeed, complex 6 is unable to coordinate to DNA, which is reflected by its incapability to carry out double-strand breaks. Nonetheless, this complex exhibits efficient DNA-cleavage activity, and its cytotoxicity is high for several cell lines. Complex 6 shows better antiproliferate activity than both cisplatin and Cu(3-Clip-Phen) toward most cancer cell lines. Furthermore, the cytotoxicity observed for 1 is for most cell lines close to that of cisplatin, or even better. Cu(3-Clip-Phen) induces very low cytotoxic effects, but a marked migratory activity. Complex 6 presents DNA-cleavage properties comparable to the one of Cu(3-Clip-Phen), but it does not show any migratory activity. Interestingly, both Cu(3-Clip-Phen) and 6 induces vacuolisation processes in the cell in contrast to complex 1 and cisplatin. Thus, the four complexes cisplatin tested, Cu(3-Clip-Phen), 1 and 6 stimulate different cellular responses.     

Continuous‐scan capability at SSRL and applications to X‐ray diffraction

Typical X‐ray diffraction measurements are made by moving a detector to discrete positions in space and then measuring the signal at each stationary position. This step‐scanning method can be time‐consuming, and may induce vibrations in the measurement system when the motors are accelerated and decelerated at each position. Furthermore, diffraction information between the data points may be missed unless a fine step‐scanning is used, which further increases the total measurement time. To utilize beam time efficiently, the motor acceleration and deceleration time should be minimized, and the signal‐to‐noise ratio should be maximized. To accomplish this, an integrated continuous‐scan system was developed at the Stanford Synchrotron Radiation Lightsource (SSRL). The continuous‐scan system uses an in‐house integrated motor controller system and counter/timer electronics. SPEC software is used to control both the hardware and data acquisition systems. The time efficiency and repeatability of the continuous‐scan system were tested using X‐ray diffraction from a ZnO powder and compared with the step‐scan technique. Advantages and limitations of the continuous‐scan system and a demonstration of variable‐velocity continuous scan are discussed.     

Enzyme-purification and catalytic transformations in a microstructured PASSflow reactor using a new tyrosine-based Ni-NTA linker system attached to a polyvinylpyrrolidinone-based matrix

The synthesis of a Ni-nitrilotriacetic acid (Ni-NTA) attached via a new tyrosine-based linker matrix on monolithic crosslinked poly(vinyl benzyl chloride)/poly(vinylpyrrolidinone) is described. This matrix is incorporated inside a microstructured PASSflow reactor which was used for automatic purification and immobilisation of His(6)-tagged proteins. These could be used as stable and highly active biocatalysts for the synthesis of (R)-benzoin (6), (R)-2-hydroxy-1-phenylpropan-1-one (7) and 6-O-acetyl-D-glucal (17) in a flow-through mode.     

High-performance thin-layer chromatography method for quantitative determination of oenothein B and quercetin glucuronide in aqueous extract of Epilobii angustifolii herba

A method was developed for separation and quantitative determination of oenothein B (OeB) and quercetin glucuronide (QG) in aqueous extract of Epilobii angustifolii herba by HPTLC-densitometry. The analyses were performed on HPTLC RP-18 WF(254) plates with 25% MeCN in water (+50mM H(3)PO(4)) as the mobile phase (distance of 8 cm) for OeB quantification and then with acetonitrile (distance of 4 cm) for QG quantification. OeB and QG were determined by densitometry at 270 and 350 nm, respectively. Their amounts were calculated using the regression equations of the calibration curves which were linear in a range of 1.14-2.28 microg spot(-1) for OeB and of 0.0768-0.6912 microg spot(-1) for QG. The amounts of OeB and QG in aqueous extract of Epilobii angustifolii herba measured by the method developed were 152.46+/-4.92 and 22.07+/-1.38 mg g(-1), respectively. The method was found to be relatively simple, specific, precise and accurate for the quality control of Epilobium angustifolium extracts.     

New calamenene sesquiterpenes from Tarenna madagascariensis

Four calamenene sequiterpenes, (+)-(7R,10S)-15-hydroxycalamenene (3), (+)-(7R,10S)-2,15-dihydroxycalamenene (4), (+)-(7R,10S)-2-hydroxy-15-calamenal (5), (+)-(7R,10S)-15-calamenal (6), along with the amorphane sesquiterpene (+)-(1S,6R,7R,10S)-1-hydroxy-3-oxo-amorph-4-ene (16), have been isolated from the Madagascan shrub Tarenna madagascariensis (Rubiaceae) and their structures determined by spectroscopic methods and chemical correlations. Furthermore, five known related sesquiterpenes [(+)-(7R,10S)-2-hydroxycalamenene (1), (+)-(7R,10S)-3-hydroxycalamenene (2), (-)-alpha-cadinol (13), cadinenal (14), 6-epicadinenal (15)], and three known lignans [(-)-hinokinin, (-)-dihydrocubebin, (-)-cubebin] were also isolated from the same plant. This is the first report of compounds 3, 4, 5, 6, and 16 from a natural source.     

New terpenoids from two Indonesian marine sponges

A C16 norsesterterpenoid (euplectellodiol, 1) and a norditerpenoid (2) have been isolated from the marine sponges Mycale euplectelloides and Diacarnus megaspinorhabdosa, respectively. Their structures have been determined by spectroscopic methods. Compounds 1 and 2 are new natural products.     

A Noise Temperature Analysis of the Electrical Degradation of Thin Nanostructured Films

Thermal noise measurements at proper biasing conditions are shown to represent a powerful tool for the characterization of the homogeneity of thin nanostructured films and their adhesion to the substrate. By modeling a thin-film as a two-dimensional random resistor network, we introduce a new type of excess-noise arising from local sources of Nyquist noise due to the presence of defective regions. The dishomogeneous Joule heating of the film is responsible for a thermal and electrical instability which is efficiently described by using a biased percolation model. The results of our simulations show that the Nyquist excess-noise temperature should provide a sensitive and non-destructive indicator of the packing density and of the quality of heat contact to the substrate of nanostructured films with grain size in the range 10–500 nm.     

On the Non‐Hierarchical Preconditioner Constructions

In this paper a new cyclic matrix representation of the H^–1/2 norm is presented. Its application as Schur complement preconditioning matrix requires only matrix‐vector multiplication. The computational cost of this matrix‐vector multiplication is O (N · log(N)) arithmetic operations, where N is the number of unknowns. The efficiency of the construction to elliptic problems has been verified by numerical tests. (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

Quick and sensitive HPLC separations on non-porous reversed-phase packings

Summary The aim of this work was to evaluate reversed-phase chemically bonded non-porous (micropellicular)d _p=1.5 μm stationary phases. On these modern phases the time for analysis of complex mixtures of solutes—whether monomeric or polymeric (e.g. drugs, vitamins, peptides, or protein)—is very short compared with that on porous phases. Different surface chemistries were elaborated for the separation of different types of sample. For the separation of small molecules a long-chain (C₁₄) hydrocarbon-coated phase seems to be optimum; a short chain (C₆) hydrocarbon bonded to the surface of the silica seems better for the separation of polymers. The efficiency, the low analysis times, and sensivities were demonstrated by separation of different proteins, peptides, drugs, alkaloids, and mixtures of water and fat-soluble vitamins.     

Adsorption and reactions of CH2I2 on Ru(001) surface

The adsorption and dissociation of CH₂I₂ were studied at 110 K with the aim of generating CH₂ species on the Ru(001) surface. The methods used included X-ray photoelectron spectroscopy (XPS), ultraviolet photoelectron spectroscopy (UPS), temperature programmed desorption (TPD), Auger electron spectroscopy (AES) and work function measurements. Adsorption of CH₂I₂ is characterized by a work function decrease (0.96 eV at monolayer), indicating that adsorbed CH₂I₂ has a positive outward dipole moment. Three adsorption states were distinguished: a multilayer (T_p=200 K), a weakly bonded state (T_p=220 K) and an irreversibly adsorbed state. A new feature is the formation of CH₃I, which desorbs with T_p=160 K. The adsorption of CH₂I₂ at 110 K is dissociative at submonolayer, but molecular at higher coverages. Dissociation of the monolayer to CH₂ and I proceeded at 198–230 K, as indicated by a shift in the I(3d_5/2) binding energy from 620.6 eV to 619.9 eV. A fraction of adsorbed CH₂ is self-hydrogenated into CH₄ (T_p=220 K), and another one is coupled to di-σ-bonded ethylene, which — instead of desorption — is converted to ethylidyne at 220–300 K. Illumination of the adsorbed CH₂I₂ initiated the dissociation of CH₂I₂ monolayer even at 110 K, and affected the reaction pathways of CH₂.